Hope for Brain Tumors: New Drug With Miami Roots Emerges
Summary
- A new drug tested at Sylvester Comprehensive Cancer Center is generating encouraging results for patients with low-grade gliomas.
- The investigation tested vorasidenib in patients whose brain tumors show mutations in the IDH1 or IDH2 genes.
- Patient survival without tumor progression was significantly better in the vorasidenib group than in the placebo group.
A new drug tested at Sylvester Comprehensive Cancer Center, part of UHealth — the University of Miami Health System, is generating encouraging results for patients with low-grade gliomas.
The international study, whose co-authors include Macarena De La Fuente, M.D., associate professor in the Division of Neuro-oncology at the University of Miami Miller School of Medicine, chief of neuro-oncology at Sylvester and co-director of the Sylvester Brain Tumor Institute, was published two years ago in The New England Journal of Medicine.
The results are now bearing fruit.
Investigating Grade 2 Gliomas and Vorasidenib
The investigation tested vorasidenib in patients whose brain tumors show mutations in the IDH1 or IDH2 genes. Up to 80% of all patients with grade 2 gliomas have these mutations. The trial included more than 300 participants from 10 countries: the United States, Canada, several European nations, Australia and Israel.
Vorasidenib is designed for patients who have already undergone biopsy or surgery to remove some or all of their tumor. The pill is taken daily.
One of the participants in the study, Brian Loy of Melbourne, Fla., is a patient of Dr. De La Fuente.
“The results of this clinical trial are changing the way we treat gliomas,” said Dr. De La Fuente. “My colleagues in the field and I are very excited about this development.”
When Loy, 42, was diagnosed with a low-grade glioma in late 2019, Ricardo Komotar, M.D., professor of clinical neurological surgery and co-director of the Sylvester Brain Tumor Institute, removed most of the tumor. It wasn’t possible to remove it all. That course would have caused permanent damage, a common problem in these cases.
The care team could have recommended watchful waiting, followed by chemotherapy or radiation, if scans showed tumor growth.
But for the preceding decade, Dr. De La Fuente had been investigating IDH inhibitors, which can help stop tumors with these mutations from growing. One of the drugs, vorasidenib, was experimental at the time. It targeted the type of mutation that Loy had, so Dr. De La Fuente asked if he wanted to take part in a phase 3 study of the medication.
Phase 3 studies are crucial in the life of a potential new drug. Success means the drug has passed safety and effectiveness tests in the first two phases and can be made available to patients if approved by regulators.
Loy agreed to participate.
“We have a young family,” he said. “The side effects of radiation or chemo would have been very disruptive to the kind of normal life we’re trying to give the children.”
Following the study’s protocol, Loy was eligible to enroll after a year of no tumor growth.
“This was a randomized study,” Dr. De La Fuente said. “Patients either received vorasidenib or a placebo, which is basically a pill with no medical value.”
Patient Survival Without Tumor Progression
The results were dramatic. Patient survival without tumor progression was significantly better in the vorasidenib group than in the placebo group, 27.7 months versus 11.1 months.
The researchers were so encouraged they ended the study early, allowing placebo patients to receive the actual drug. The FDA approved vorasidenib in August 2024 for use in patients with tumors showing IDH1 or IDH2 mutations.
Loy was in the vorasidenib group. Over the course of the study, his seizures became less frequent and he had no headaches or vision problems. In fact, he has now gone a full year without a seizure.
“This is huge progress, and I’m very grateful,” he said. “We tried a few different combinations of anti-seizure meds with the vorasidenib and found the right recipe. There will always be that possibility of more seizures as long as the tumor is there, but what we have now seems to be working well.”
Breaking Through the Blood-Brain Barrier
Even more encouraging, follow-up MRIs showed the tumor was shrinking. In addition to impressive results, vorasidenib is unique in other ways.
“Most drugs we use to treat cancer don’t reach the brain in therapeutic amounts,” said Ashish Shah, M.D., assistant professor of neurological surgery at the Miller School. “Only a handful can break through the blood-brain barrier at what we call relevant concentrations — enough to actually make a difference. Vorasidenib does just that. So, unlike with other drugs, physicians don’t have to increase the dosage for the medication to eventually reach the brain, which could have a harmful effect on other organs.”
Loy continues to take vorasidenib daily, with regular checkups and scans.
“We have patients who started taking similar drugs 10 years ago who continue to do well,” Dr. De La Fuente said. “I’m hopeful Brian will be one of them also.”
For Dr. De La Fuente, witnessing the twisting journey from preliminary lab studies to real-life results has been extremely gratifying.
“People ask me how I do this work,” she said. “But when I see the results of studies such as this, when I see patients like Brian doing so well, it reminds me of why we do it. This is what gives our work meaning.”
Tags: brain cancer, brain tumors, Dr. Ashish Shah, Dr. Macarena De La Fuente, gene therapy, glioma, Sylvester Brain Tumor Institute, Sylvester Comprehensive Cancer Center